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Study of Oral LBH589 in Adult Participants With Refractory/Resistant Cutaneous T-Cell Lymphoma (CTCL)

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ClinicalTrials.gov Identifier: NCT00490776
Recruitment Status : Terminated (Recruitment was stopped on 15 June 2009 (early termination date) due to low prevalence of study population and slow accrual.)
First Posted : June 25, 2007
Results First Posted : June 18, 2021
Last Update Posted : August 18, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This study evaluated the safety and efficacy of LBH589B in adult participants with refractory/resistant Cutaneous T-Cell Lymphoma and prior Histone Deacetylase (HDAC) inhibitor therapy.

Condition or disease Intervention/treatment Phase
Cutaneous T-Cell Lymphoma Drug: Panobinostat Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Oral LBH589 in Adult Patients With Cutaneous T-Cell Lymphoma Who Are Intolerant to or Have Progressed on or After Prior HDAC Inhibitor
Actual Study Start Date : July 5, 2007
Actual Primary Completion Date : September 2009
Actual Study Completion Date : September 22, 2009


Arm Intervention/treatment
Experimental: Panobinostat 20 mg
Participants received panobinostat, 20 milligrams (mg), capsules, orally, thrice weekly on alternate Days 1, 3, and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression, and/or physician's discretion to discontinue the treatment.
Drug: Panobinostat
Panobinostat, 20 mg, hard gelatin capsules, orally, thrice weekly.
Other Name: LBH589




Primary Outcome Measures :
  1. Overall Response Rate (ORR) in Participants With Resistant Cutaneous T-Cell Lymphoma (CTCL) Treated With Oral Panobinostat by Using the Modified Severity-Weighted Assessment Tool (mSWAT) [ Time Frame: From first dose of study drug up to disease progression or death, (up to approximately 2 years) ]
    ORR was defined as the percentage of participants with best overall response (OR) of complete response (CR) or partial response (PR) based on mSWAT score, (OR = CR + PR). mSWAT score represents the product of the percentage total body surface area (%TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: modified SWAT score = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 4). The sum of these 3 numbers gave the modified SWAT score, on a 0 (no lesions) to 400 (lesions covering all areas) scale. CR based on mSWAT score was defined as the absence of skin disease. PR was defined as ≥ 50% decrease of the modified SWAT score compared to the Baseline score.


Secondary Outcome Measures :
  1. Response Rate of Participants With Refractory CTCL Using the Physician's Global Assessment of Clinical Condition (PGA) [ Time Frame: From first dose of study drug up to disease progression or death, (up to approximately 2 years) ]
    Response rate was defined as the percentage of participants with CR or PR based on PGA scale. PGA is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the participant's disease as compared to Baseline. CR corresponds to Grade 0 (Completely clear) on PGA scale and was defined as no evidence of disease; 100% improvement. PR corresponds to Grade 2 (marked improvement) on PGA scale and was defined as significant improvement (≥75% - <90%); some evidence of disease remains.

  2. Response Rate in Participants With Refractory CTCL Using Modified Skin Score [ Time Frame: From first dose of study drug up to disease progression or death, (up to approximately 2 years) ]
    Response rate was defined as the percentage of participants with CR or PR based on mSWAT skin score. mSWAT score represents the product of the %TBSA involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: mSWAT score = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 4). The sum of these 3 numbers gave the modified SWAT score, on a 0 (no lesions) to 400 (lesions covering all areas) scale. CR based on mSWAT score was defined as the absence of skin disease. PR was defined as ≥ 50% decrease of the modified SWAT score compared to the Baseline score.

  3. Responses in Index Lesions in Participants With Refractory CTCL by Lesion Measurements With Photographic Supporting Documentation [ Time Frame: From first dose of study drug up to disease progression or death (up to approximately 2 years) ]
    Index lesions in each participant were selected as four to six of the prominent lesions amenable to bi-dimensional measurements. The longest diameter and its perpendicular measurement were used to determine the surface area and a weighted sum was determined as: Lesion 1 + lesion 2 + … + lesions 6 = Total sum of weighted score where Lesion 1: cm^2 x [1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)]; Lesion 2: cm^2 x [1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)]; Lesion 6: cm^2 x [1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)]. These lesions were photographed at Baseline and at the time of response determined by either mSWAT or PGA

  4. ORR of Participants With Resistant CTCL Treated With Oral Panobinostat by Using the Modified PGA to Assess Skin Disease and the Evaluation of Disease in the Viscera, Lymph Nodes and Blood (Circulating Sézary Syndrome Cells) [ Time Frame: From first dose of study drug up to disease progression or death, (up to approximately 2 years) ]
    ORR was defined as the percentage of participants with best OR of CR or PR based on PGA scale (OR = CR + PR). The PGA is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the participant's disease as compared to Baseline. CR corresponds to Grade 0 (completely clear) of PGA scale and was defined as no evidence of disease; 100% improvement. PR corresponds to Grade 2 (marked improvement) of PGA scale and was defined as significant improvement (≥75%-<90%); some evidence of disease remains.

  5. Duration of Response (DOR) [ Time Frame: From first dose of study drug up to disease progression or death, (up to approximately 2 years) ]
    DOR was defined as the time from first documented evidence of CR or PR until the earliest date of documented progression or death due to any cause among participants who achieved a confirmed CR or PR. The DOR was calculated in two ways. The DOR among responders only included participants who responded to the drug. The overall DOR included non-responders as having a DOR of zero days.

  6. Time to Response (TTR) [ Time Frame: From first dose of study drug up to study completion (approximately 2 years) ]
    TTR was defined as the time from the start of treatment until the first documented evidence of CR or PR among participants who achieved a confirmed CR or PR.

  7. Progression-Free Survival (PFS) [ Time Frame: From first dose of study drug up to disease progression or death, (up to approximately 2 years) ]
    PFS was defined as the time from the start of treatment until the earliest date of disease progression or death due to any cause, if sooner.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Written informed consent obtained prior to any screening procedures
  2. Age greater than or equal to 18 years old
  3. Participants with biopsy-confirmed stages IB-IVA mycosis fungoides or Sézary syndrome (SS). Participants with SS who have bone marrow involvement are also eligible. Participants with transformed CTCL are eligible
  4. Participants must have been treated with an HDAC inhibitor given for the treatment of CTCL. Participants must have had disease progression on or following treatment with an HDAC inhibitor. Participants are also eligible if they had an inadequate response to an HDAC inhibitor defined as stable disease as the best response after at least 3 months of therapy. Participants previously treated with an HDAC inhibitor are also eligible if they experienced intolerance due to adverse events.
  5. Baseline multiple-gated acquisition scan (MUGA) or echocardiogram must have demonstrated left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal
  6. ECOG performance status ≤ 2

Exclusion criteria:

  1. Participants with a history of visceral disease including central nervous system (CNS) involvement (i.e. stage IVB CTCL). Note, participants who have SS with bone marrow involvement are eligible
  2. Impaired cardiac function
  3. Concomitant use of drugs with a risk of causing torsades de pointes
  4. Participants who have received chemotherapy or any investigational drug or undergone major surgery ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  5. Less than 3 months since prior electron beam therapy
  6. Women who are pregnant or breast feeding, or women of childbearing potential (WOCBP) not willing to use a double method of contraception during the study and 3 months after the end of treatment.

Other protocol-defined inclusion/exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00490776


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00490776    
Other Study ID Numbers: CLBH589B2212
First Posted: June 25, 2007    Key Record Dates
Results First Posted: June 18, 2021
Last Update Posted: August 18, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Cutaneous T-Cell Lymphoma
adults
Mycosis Fungoides
Sézary Syndrome
CTCL
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Panobinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action